Starting on the A5 at Hockliffe the road ran northwards, roughly parallel to the A5, although the two roads diverged constantly. There were brief multiplexes at Woburn and Newport Pagnell before the A506 ended on the A508 to the south of Northampton.

In 1935, the entire road became a southern extension of the A50. However, by the 1970s it had become downgraded again to a variety of roads and no longer forms a coherent through route. The section through Milton Keynes still exists but is unclassified.